The Current Wave in the Biopharmaceutical Industry.pptx.pptx

The Current Wave in the Biopharmaceutical Industry

1. Biosimilars: The Current Wave in the Biop harmaceutical Industry

2. Our mission and our values OUR MISSION: To serve patients by proving affordable biosimilars at 50-60 % lesser than the innovative products and 20-30% lesser than the existing biosimilars that have the power to restore health or even save lives. OUR VALUES: Be science based and quality based Create value for patients and employees Be ethical and Trust and respect each other Collaborate, communicate and accountable

3. Biosimilars Definition: The products must be bioequivalent or comparable to the original innovative products in terms of preclinical, PK/PD as well as safety and efficacy. Follow-on innovators products, developed by parties other than original developers using either identical or different manufacturing processes. Biosimilars / Bio generics /Follow on Biologics / Follow on Proteins all represents the same.

4. A Trend Towards Biological Pharmaceuticals

5. Top 15 biosimilars   Product 2014 ($m) 2013 ($m) Growth ($m) Growth (%) 1 Humira 13021 11105 1916 17 2 Sovaldi/Harvoni 12410 139 12271 8828 3 Remicade 10151 9900 251 3 4 Enbrel 9120 8894 226 3 5 Lantus 8152 7343 809 11 6 MabThera/Rituxan 7356 7410 -54 -1 7 Avastin 6841 6667 174 3 8 Seretide/Advair 6700 8356 -1656 -20 9 Herceptin 6690 6481 209 3 10 Crestor 6617 6960 -343 -5 11 Abilify 6416 9502 -3086 -32 12 Lyrica 5435 4838 597 12 13 Revlimid 4980 4280 700 16 14 Gleevec/Glivec 4746 4693 53 1 15 Spiriva 4722 4564 158 3

6. Top 10 projected products in 2015

7. Future biopharmaceutical products

8. Patent Expiries-the Opportunity Driver

9. Top Ten Players in Biotechnology Field Amgen Roche/Genentech Johnson & Johnson Novo Nordisk Lilly Sanofi-Aventis Abbott Serono (Merck) Schering Plough •Wyeth

10. Key Players in Biosimilars Hospira Teva Sandoz Barr Lab Biocon Dr. Reddys Cangene Intas pharmaceuticals Zydus cadila, Reliance life sciences etc,,.

11. Challenges for Biosimilars Development

12. Challenges for Biosimilars Development High cost, longer term Technology derived Complicated analytical techniques “innovative like” clinical studies Effective brand patent protection for over 20 years Enter the market at risk (no paragraph IV) No inter changeability, brand marketing required Injectable manufacturing capability Microbial and Mammalian cell fermentation facilities in large scale Overall, high barriers to entry, but high margin Public demanding for affordable biological drugs

13. It Is Not the Generics We Know

14. How Are the Bio products Made Generally?

15. How Is a Biosimilars Product Developed? Upstream –Cell line development –Fermentation Downstream –Purification –Fill and Finish Comprehensive analytical characterization and comparability study •Clinical study –Preclinical –Clinical Submission

16. 1. Cell Line Development (The Fundamental) Analyze the DNA sequence of the targeted protein based on the published literature information Synthesize the cDNA Construct the vector Transfer the vector into the cell Positive cell line screening and selection High yield cell line selection Cell bank characterization and storage Master cell bank and working cell bank

17. 2. The Fermentation Process Development Bioreactor selections Culture medium optimization High yield culture conditions Process scale up (difficulty), extensive comparability study need to be done

18. 3. Protein Purification Cell breakage Removal of cells Capture of proteins Removal of virus Primary purification Secondary purification Lyophilisation of purified proteins Characterization

19. Upstream and downstream flow chart

20. 4. Fill Finish Formulation development Freezing/thawing impact Manufacturing process development Mixing and holding time Filter compatibility Microbial retention Lyo cycle development Package selection Device development Stability testing

21. Injecting Devices for Bio products

22. 5. Comprehensive and Orthogonal Analytical Analysis and Comparability (the 2ndmost important aspect)

23. 5. Comprehensive and Orthogonal Analytical Analysis and Comparability (the 2ndmost important aspect) Primary Structure: Peptide mapping AA analysis including D/L AA N and C terminal sequencing Isoforms Glycosylation analysis MS Related substances and degradation products Charge variants Size variants

24. 5. Comprehensive and Orthogonal Analytical Analysis and Comparability (the 2ndmost important aspect) Secondary Structure Alpha helix Beta sheets NMR DSC CD Tertiary and Quaternary Structure Light scattering Analytical Ultra centifugation (AUC) SEC Field Flow Fraction (FFF) Atomic Force Microscopy (AFM) In-vitro and In-Vivo Bioassay ELISA

25. 5. Extensive Comparability Study With innovator products When cell line changes When culture medium changes When culture condition changes When master and working cell bank generation changes When fermentation process changes When scaled up When facility changes Using stressed samples

26. 6. Clinical Trials (Lengthy and Expensive) Preclinical study Toxicology in animals Phase I Study PK/PD in healthy subjects Phase III Study Safety/Efficacy All indications In patients Immunogenicity study Post-market monitoring

27. 7. Submissions No clear regulatory pathway in US. Product specific in EU FDA treat it as BLA Pre-IND meetings and scientific advisory meeting are needed Expensive submission fee

28. OUR STRATEGY

29. Summary Biosimilars are the trend Have drawn extensive attentions from public, regulatory bodies, governments and certainly pharmaceutical companies Challenging, cost, but worth to develop Has created huge opportunities for the organizations and CRO who are engaged in the Analysis and Characterizations of Biological Molecules and cell culture

30. Thank you Do not miss this wave and opportunity